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Improved formulation of W/O/W multiple emulsion for insulin encapsulation. Influence of the chemical structure of insulin

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Abstract

W/O/W multiple emulsions are systems of potential interest in the oral administration of insulin. Although it has been shown that a single oral administration of insulin-loaded W/O/W multiple emulsion to diabetic rats led to the significant decrease of blood glucose levels (Silva Cunha et al., 1998, Int J Pharm 169:33), repeated administrations displayed unpleasant side effects such as diarrhoea and steatosis. These unwanted effects were attributed to the high oil concentration used for their preparation. In the present study, attention was focused on the reduction of oil concentration in the formulation of these systems and on the encapsulation of two different insulins. The physical properties and stability of the multiple emulsions over long periods of time were assessed by conductivity measurements, and granulometric and microscopic analyses. The encapsulation in the inner aqueous phase of two insulins, Umulin and Humalog, differing only by the transposition of one amino acid, had non-negligible effects on the formation and stability of W/O/W multiple emulsions. Both insulins were shown to improve the formation of the multiple emulsions. Circular dichroism studies and surface tension measurements evidenced the contribution of insulin conformation and surface properties in multiple emulsion formation and stability.

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Acknowledgements

We are indebted to the Eli Lilly Company (Indianapolis, USA) for a generous supply of insulin and to Goldschmit (France) for the supply of Abil EM-90. Fabienne Cournarie is very grateful to the "Chancellerie des Universités de Paris" for the financial support.

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Authors and Affiliations

  1. Laboratoire de Physico-chimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Faculté de Pharmacie, Université Paris XI, 5 rue Jean-Baptiste Clément, 92296 Cedex, Châtenay-Malabry, France

    Fabienne Cournarie, Véronique Rosilio, Christine Vauthier, Jean-Louis Grossiord & Monique Seiller

  2. UMR CNRS 7033, case 138, Laboratoire de Physico-chimie Biomoléculaire et Cellulaire, 4 place Jussieu, 75252 Cedex 05, Paris , France

    Monique Chéron

  3. Laboratoire de Physiologie, UPRES 2706, Faculté de Pharmacie, Université Paris XI, 5 rue Jean-Baptiste Clément, 92296 Cedex, Châtenay-Malabry , France

    Bernard Lacour

Authors
  1. Fabienne Cournarie
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  2. Véronique Rosilio
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  3. Monique Chéron
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  4. Christine Vauthier
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  5. Bernard Lacour
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  6. Jean-Louis Grossiord
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  7. Monique Seiller
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Corresponding author

Correspondence to Jean-Louis Grossiord.

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Cournarie, F., Rosilio, V., Chéron, M. et al. Improved formulation of W/O/W multiple emulsion for insulin encapsulation. Influence of the chemical structure of insulin. Colloid Polym Sci 282, 562–568 (2004). https://doi.org/10.1007/s00396-003-0960-8

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  • DOI: https://doi.org/10.1007/s00396-003-0960-8

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